Healthy Behaviors May Help Stressed Cells Stay Young

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In healthy women followed for over 1 year, accumulation of major life stressors predicted telomere attrition.

Women who maintained relatively higher levels of health behaviors appeared to be protected when exposed to stress.

Major life stressors appear to be associated with significant acceleration of cellular aging over a relatively short period of time, but engaging in healthy behaviors such as eating well, exercising regularly, and getting enough sleep may mitigate that effect, a study showed.

Researchers examined the interaction between stressors like divorce or caring for an elderly parent and cellular aging, measured by telomere shortening, during a 1-year period in a cohort of middle-age women. The observational study is the first to examine short-term changes in telomere length in relation to stress, lead researcher Eli Puterman, PhD, of the University of California San Francisco, and colleagues wrote in the journal Molecular Psychiatry.

While telomere length did not change drastically over the course of the year in the majority of women, there was still a significant amount of change and that change was predicted by life stressors and modifiable healthy behaviors.

The findings support the idea that stressful events can quickly lead to acceleration of immune cell aging in adults and that healthy behaviors can protect cells from this assault, Puterman said.

"In our sample of participants who were eating well, sleeping well, and exercising regularly over the course of the year, the amount of stress they experienced did not seem to impact telomere length," he told MedPage Today.

Telomeres: Chromosomal Aglets

The UCSF research team included Elizabeth H. Blackburn, MD, who was awarded a Nobel Prize in Medicine in 2009 for her role in discovering the molecular nature of telomeres, which help protect the genetic information in eukaryotic chromosomes from degrading.

Telomeres have been compared to plastic tips on shoelaces known as aglets, because they keep chromosome ends from fraying. Fraying degrades chromosomes by promoting incomplete replication, exogenous and endogenous damage, and detrimental fusion during DNA repair.

In humans, telomeres consist of repeated sequences (TTAGGG repeats) of DNA that are thousands of nucleotides long, encapsulated and stabilized by associated proteins. Short telomeres have been linked to many diseases of aging and when telomeres shorten to a critical length, cells typically enter senescence, the researchers wrote.

Chronic psychological stress has been associated with cell aging as measured by shorter telomeres in multiple cross-sectional studies, but the newly published research is the first to prospectively examine telomere length change related to stress over a short period, Puterman said.

Major Life Stressors Included Job Loss, Divorce

The study included 263 healthy, middle age women (between age 50 and 65 at enrollment) living in San Francisco and enrolled between February and May of 2010. All were nonsmokers with no history of cancer or autoimmune disease.

Blood samples were taken from all the women at the beginning of the study in the summer of 2010, and blood was taken again 1 year later in the summer of 2011. Ninety-one percent (n=239) of the women returned for the follow-up blood draw.

Health behaviors at study entry and again at 4 months, 8 months and 1 year follow-up were self reported and included leisure-time physical activity (measured using the Stanford Brief Activity Scale), typical dietary practices (measured using a validated food-frequency questionnaire), and sleep quality (participants were asked to rate their sleep quality on a scale of 1 to 5, with 1 being 'very bad' and 5 being 'very good.'

Major life stressors were self reported at the 1-year follow-up using a 13-item checklist for major adverse events.

Stressors included loss of household, major financial difficulties, self or family member employment loss, continued unemployment and job searching, relationship problems including divorce, ongoing arguments with a close relative or friend, care giving for an adult or child with serious illness, death of a family member or close friend, and sexual harassment.

Complete data on stressors and health behaviors were available for 231 women.

To test the hypotheses that life stressors and lifestyle would impact telomere length over this short period, leukocyte telomere length (LTL) change (LTL from baseline subtracted from 1 year follow-up) was first regressed on major life stressors with covariates including various socioeconomic factors, education, medication use, and BMI.

A series of regression analyses were completed with the interaction between major life stressors and each health behavior alone assessed (while co-varying the two other behaviors) and cumulative health behaviors as a combined factor.

Stressors Predicted Accelerated Shortening

The women in the study were overwhelmingly white, highly educated, and economically advantaged. A total of 84% had college degrees, 54% earned more than $100,000 a year, and 84% were Caucasian. The average baseline BMI was in the normal-weight range of 24.19 (SD=4.59) and medication use was minimal, with the exception of hormone replacement therapy (HRT=42%, blood pressure meds=15%, statins=10% and antidepressants=17%.

At baseline, mean leukocyte telomere length was 5548 base pairs (SD=328.9), which was similar to the 12-month follow-up length of 5584 base pairs (SD=354.9). Baseline and follow-up telomere length were significantly related (r (229)=0.74, P<0.001), indicating considerable stability over time. The average percent change was minimal (0.65%) with a standard deviation for percent change in telomere length of 4.86%.

"As would be expected for a short period of 1 year, the majority of people (68%) did not show a large increase or decrease greater than approximately 5% of their baseline telomere length," the researchers wrote.

At 1 year follow-up, the distribution of stressors was as follows: 32% experienced the death of a family member or close friend, 26% women reported that they experienced relationship difficulties, 20% were involved in care giving, 17% became unemployed or experienced financial strain, 4% experienced sexual harassment, and 3% experienced loss of their house.

Thirty-seven percent of women did not have any major life events over the study year, 47% had one or two, and 16% experienced three or more.

Major stressors during the year significantly predicted accelerated telomere shortening over the same time frame, suggesting that for every one event, there was a significantly greater decline in telomere length over the year of 3.47 base pairs (standard error=14.04, 95% CI=-62.3, -6.9).

Different regression equations examining the covariates, major life stressors, and each of three health behaviors tested whether each behavior alone moderated the relationship between major life stressors and telomere shortening.

At one standard deviation below the mean and at the mean of each behavior separately, major life stressors significantly predicted telomere shortening. At one standard deviation above the mean of each health behavior, life stressors were unrelated to telomere shortening. The interaction effects for the three moderation analyses were not statistically significant, however (all interaction P's >0.10).

Healthy Lifestyle Protected Against Stress Loss

The average person has a telomere length of around 10,000 base pairs at birth, and researchers estimate that each year of life people lose from 20 to 60 base pairs.

Puterman said their research indicates that each major life stressor results in an extra loss of around 40 base pairs annually, roughly doubling the yearly expected loss. People with poor diets, exercise, and sleeping habits lost, on average, an extra 75 base pairs per year, while life stressors did not seem to affect telomere length in people who ate well, slept well, and exercised.

"From what we know about the impact of these (healthy) behaviors on cells, it appears that all three are important protectors against cellular aging," he said.

The UCSF researchers are now recruiting for an interventional study that will focus on exercise. Puterman said they hope to recruit 80 caregivers of family members with Alzheimer's disease. Half will receive gym memberships, weekly coaching sessions, and other motivations to increase exercise for 6 months, and the other half will receive no intervention.

The goal is to determine if regular exercise impacts telomere length over this short period in these highly-stressed people, he said.

Limitations cited by the researchers included the observational, self-reported design of the study and the homogeneity of the study population.

They also noted that the extent to which the effects of stress on telomere biology are reversible may depend on how long stressors remain.

"Lifespan studies that combine factors from early life and adulthood experiences together with health behaviors are needed to examine adequate doses for reversing the damage of accumulated stress across the lifespan," they wrote.

In a written press statement, Blackburn said interventional studies to test the impact of healthy lifestyle and stress on cell aging are needed.

"These new results are exciting yet observational at this point," she noted. "They do provide the impetus to move forward with interventions to modify lifestyle in those experiencing a lot of stress, to test whether telomere attrition can truly be slowed."

The study was supported by the Baumann Foundation and the Barney & Barbro Foundation.

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